Detection of ARv7 in the Plasma of Men With Advanced Metastatic Castrate Resistant Prostate Cancer (MCRP)

Demonstrate detection of ARv7 splice variant transcripts from exosomes in the circulation of MCRPC patients pre and post treatment with selective Androgen pathway inhibitors (i.e. abiraterone and enzalutamide)

Study Overview

• Status: Suspended
• Conditions: Metastatic Castrate Resistant Prostate Cancer

Detailed Description

Primary Objective

-Demonstrate detection of ARv7 splice variant transcripts from exosomes in the circulation of MCRPC patients pre and post treatment with selective Androgen pathway inhibitors (i.e. abiraterone and enzalutamide)

Secondary and Exploratory Objectives

• Correlate ARv7 status with PSA response (>/=50% decline in PSA level from baseline, maintained for >/=4 weeks) at any time after the initiation of therapy.
• Comparison of median progression free survival (PFS) and overall survival (OS).
• Determine additional molecular lesions in exoRNA and cfDNA in MCRPC patients post-treatment with androgen pathway inhibitors.
• Correlate other AR-variants (non ARv7) with clinical outcomes including PSA response.

• Study Type: Observational
• Enrollment (Anticipated): 30

Contacts and Locations

Study Locations

• United States
  • Connecticut
    • New Haven, Connecticut, United States, 06520
      • Yale University School of Medicine

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: Male

• Sampling Method: Probability Sample

Study Population

Community sample

Description

Inclusion Criteria:

1. Participants must have histologically confirmed diagnosis of adenocarcinoma of the prostate.
2. Clinical or radiographic evidence of metastatic disease.
3. Planned therapy with either enzalutamide or abiraterone acetate within the coming 6 weeks.

4. Evidence of disease progression on or following most recent therapy as evidenced by the following:

   • Radiographic evidence of disease progression as defined by one or more new bone scan lesions.
   • Growth of soft tissue / visceral metastases to greater than one centimeter in longest diameter.
   • Progressive disease despite 'castration levels' of serum testosterone (<50ng/dL with continued androgen deprivation therapy.

5. At least two of the following high risk features during screening for rapid disease progression:

   • Anemia with a hemoglobin <12.0 g/dL
   • Elevated alkaline phosphatase
   • High lactate dehydrogenase (LDH)
   • Presence of visceral metastasis on imaging
   • Presence of clinically significant pain requiring opioid analgesics.
   • PSA doubling time under 3 months on most recent therapy
   • PSA values obtained 2 or more weeks apart, with last value being 2.0ng/mL or higher.
6. Ability to understand and willingness to sign a written informed consent document.

Exclusion Criteria:

1. Receiving or intend to receive concurrent chemotherapy
2. Hepatitis (all types) in patient's medical record
3. HIV documented in patient's medical record
4. History of intercurrent or past medical history or psychiatric illness that would make participation in a blood drawing protocol difficult or not feasible.

Study Plan

How is the study designed?

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort
MCRPC; Metastatic Castrate Resistant Prostate Cancer (MCRPC) Patients

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Detection of ARv7 splice variant in the circulation of MCRPC patients. PSA response rate in ARv7 positive patients.	The detection of ARv7 splice variants in samples will be considered both binary: positive or negative/not assessable and level based. ARv7 splice variants from exosomes will be detectable from baseline in 50% of both API; PSA response rates will be 10% or less in ARv7 positive patients. With a sample of 30 patients (as reported in the NEJM study) per cohort would allow the study to have an 85% power to detect a difference of 50 percentage points in PSA response rates, with the use of a two-sided test at an alpha level of 0.1.	Two years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Detection of ARv7 splice variant in the circulation of MCRPC patients. PSA response rate in ARv7 negative patients.	The detection of ARv7 splice variants in samples will be considered both binary: positive or negative/not assessable and level based. ARv7 splice variants from exosomes will be detectable from baseline in 50% of both API; PSA response rates will be 50% or more in ARv7 negative patients. With a sample of 30 patients (as reported in the NEJM study) per cohort would allow the study to have an 85% power to detect a difference of 50 percentage points in PSA response rates, with the use of a two-sided test at an alpha level of 0.1.	Two years

Collaborators and Investigators

• Sponsor: Exosome Diagnostics, Inc.
• Collaborators: Yale University

Study record dates

Study Major Dates

• Study Start: February 1, 2016
• Primary Completion (Anticipated): December 1, 2024
• Study Completion (Anticipated): December 1, 2024

Study Registration Dates

• First Submitted: February 23, 2016
• First Submitted That Met QC Criteria: July 28, 2017
• First Posted (Actual): August 2, 2017

Study Record Updates

• Last Update Posted (Actual): October 6, 2022
• Last Update Submitted That Met QC Criteria: October 5, 2022
• Last Verified: October 1, 2022

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Genital Neoplasms, Male; Prostatic Diseases; Prostatic Neoplasms
• Other Study ID Numbers: ECT2015-004

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED